It has been recently recognized that the performance of a typical pharmaceutical is not only a function of its chemical composition, but also of its physical makeup. For example, particle sizes and distributions of both the drug and excipients play a role in the final performance of the product. These physical properties can, amongst other things, alter the dissolution profile of a drug, and result in poor or uncontrolled release of the active ingredient into a patient's bloodstream.
Typically, finished pharmaceutical products are a mixture of both the active ingredient and a variety of excipients (lactose, starch, magnesium stearate etc.). During manufacturing these components are physically blended or granulated before being pressed into their final form as tablets. Problems with blending or granulation, such as how well the components have mixed or whether or not there is an agglomeration or preferential association of one or more of the components, can have a significant impact in both the products manufacturability and ability to pass the final quality control tests before product release.
Normally both the active ingredients and the excipients are white powders and visualizing their distribution in either a powder blend, a granulation or a finished product is a challenge. Several analytical approaches are generally taken to assess the heterogeneity of the mixture or finished tablet. These include approaches such as Raman mapping and imaging spectroscopy, as well as infrared and near infrared mapping and imaging. All these approaches produce a map of the distribution of the various chemical components comprising the final product. While these approaches normally result in providing the desired information, they tend to be either slow, expensive, or both. But the information provided is so valuable for understanding an errant manufacturing process that Raman maps are sometimes acquired over a period of several days for a single tablet.